tbuckley/cabot-search huggingface dataset:
Highlights of This Issue
Journal: Clinical Cancer Research (2016)

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) and high-dose (HD) bolus interleukin-2 (IL2) have shown unprecedented rates of durable complete regression of metastatic melanoma; however, the toxicity associated with HD IL2 has hampered its widespread application. Andersen and colleagues evaluated TIL therapy in combination with an attenuated regimen of IL2 in patients with metastatic melanoma (n = 25). The authors report that classical toxicities associated with previous protocols could be reduced without compromising clinical efficacy. Interestingly, tumor regression was associated with induction and persistence of anti-melanoma T cell responses in peripheral blood. These results warrant further testing of ACT with attenuated doses of IL2 in a randomized setting.Chronic myelomonocytic leukemia (CMML) is a lethal hematologic neoplasm with no disease-modifying therapies. Preclinical studies suggest that Janus kinase 2 (JAK2) inhibition is a viable therapeutic strategy in CMML. In a phase 1 trial, Padron and colleagues tested ruxolitinib (JAK1/2 inhibitor) in CMML and found no dose-limiting toxicity at doses up to 20 mg twice daily. Significant clinical responses were observed and correlative analysis and pharmacodynamic consequences of JAK2 inhibition were reported, providing a clinical rationale for an ongoing phase II study.Baselga and colleagues analyzed whether the efficacy of trastuzumab emtasine (T-DM1) was correlated with biomarker expression in patients with HER2-positive metastatic breast cancer participating in a phase III study. Progression-free survival and overall survival were longer with T-DM1 compared with capecitabine plus lapatinib (CL) in all subgroups. PIK3CA mutations were associated with shorter median survival in CL-treated, but not T-DM1-treated, patients. These results suggest that T-DM1 is efficacious in the presence of a biomarker associated with impaired response to other HER2-targeted agents.Madore and colleagues investigated genomic, transcriptomic, and clinical correlates of programmed cell death ligand-1 (PD-L1) protein levels in melanoma patient tumor samples. PD-L1 negative tumors correlated with lower somatic mutation burden, a reduced immune response gene signature, and worse overall survival in stage III melanoma patients. PD-L1 positive tumors displayed increased expression of T cell and macrophage-specific gene sets, although negative tumors displayed reduced MHC-I antigen presentation genes. This article provides a multiplatform analysis of immune activation/dysfunction in human melanomas.
Awards, Appointments, Announcements
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Awards, Appointments, Announcements Get access JNCI: Journal of the National Cancer Institute, Volume 82, Issue 16, 15 August 1990, Pages 1319–1320, https://doi.org/10.1093/jnci/82.16.1319-a Published: 15 August 1990
Localization of the Site of Myocardial Scarring in Man by High-Frequency Components
Authors: NANCY C. FLOWERS, LEO G. HORAN, W. J. TOLLESON, J. R. THOMAS
Journal: Circulation (1969)

The increased incidence of high-frequency components (notching) in electrocardiographic (ECG) recordings previously has been related to coronary artery disease, primary myocardial disease, and biventricular enlargement. This study included 130 subjects on whom autopsy permission was obtained, who had one or more sets of high-frequency, orthogonal ECG (XYZ) leads and direct-writing standard ECG leads recorded ante mortem. In each instance careful dissection of the heart was performed by two or more of the authors according to fixed protocol. Correlations were made between the site of infarction and the occurrence of notching in specific high-frequency ECG leads. Postero-inferior infarctions tended to express themselves with a predominance of increased notching in the Y lead, while anterior infarction manifested dominantly in the X lead. This was true in intramural as well as transmural lesions. The greatest value of notch recognition in diagnosing and localizing infarction appeared to be in subjects with normal sized hearts, with none of the classic ECG criteria for infarction, but who ultimately proved to have intramural scarring. In these subjects the increased incidence of notching clearly could not be attributed to biventricular enlargement, nor could the ECG diagnosis of infarction be arrived at by conventional criteria.
Fellowships, Grants, Awards
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Fellowships, Grants, Awards Get access JNCI: Journal of the National Cancer Institute, Volume 87, Issue 21, 1 November 1995, Page 1648, https://doi.org/10.1093/jnci/87.21.1648 Published: 01 November 1995
Antibiotic Therapy for Cat-scratch Disease?
Authors: Clifford W. Bogue
Journal: JAMA (1989)

Cat-scratch disease is usually a benign, self-limited disease that causes regional lymphadenopathy. Occasionally, it may present with systemic symptoms and have a prolonged course. To date, antibiotic therapy has not been proved to be of value. We describe three patients with cat-scratch disease who were treated successfully with gentamicin sulfate. Two patients had extensive hepatic involvement, and one patient had regional lymphadenopathy. All three patients responded within 48 hours to intravenous gentamicin. Extensive follow-up has shown no recurrence of symptoms. These cases suggest that gentamicin may be efficacious in shortening the course of cat-scratch disease. Prospective, randomized trials should be performed to confirm these results. (<i>JAMA</i>. 1989;262:813-816)
Automated and Nomographic Analysis of Exercise Tests
Authors: Michael H. Sketch
Journal: JAMA (1980)

A study was conducted to evaluate the validity and usefulness of a commercially available microprocessor for automated exercise ECG analysis and to develop a nomogram for estimating the severity of coronary artery disease. Results of visual analysis, automated analysis, and coronary arteriography were correlated for the 107 patients studied. Automated analysis was shown to be valid and useful. The ST integrals (area of ST depression) recorded after exercise were superior to those recorded during exercise because they manifested higher specificity and predictive value, even though their sensitivity was slightly lower. Using postexercise integrals, it was possible to differentiate mild and severe disease. From multipleregression analysis of ST integrals, duration of exercise, and the severity of coronary artery disease, a nomogram was derived to estimate severity of coronary artery disease. (<i>JAMA</i>243:1052-1055, 1980)
Cytotoxic Antibody Complicating Platelet Support in Acute Leukemia
Authors: David Green
Journal: JAMA (1976)

Lymphocytotoxic or thrombocytolytic antibodies were detected in 11 of 25 thrombocytopenic patients receiving repeated platelet transfusions. Platelet survival times were reduced in these patients (half-life [T/2], 32 hours) as compared to patients without antibody (T/2, 51 hours,<i>P</i>&lt;.05). In one woman with acute myeloblastic leukemia and a potent platelet antibody, combination chemotherapy resulted in a profound decrease in circulating γ globulin and concurrent disappearance of the cytotoxic antibody. The survival of transfused platelets in this patient was dramatically improved, and bleeding was controlled. (<i>JAMA</i>236:1044-1046, 1976)
Highlights of This Issue
Journal: Clinical Cancer Research (2010)

Effective antitumor immunity is frequently impeded by complicating factors such as tumor-induced immune suppression via myeloidderived suppressor cells (MDSCs).Therefore, agents that inhibit MDSCs may be useful for cancer patients.Kodumudi and colleagues found that docetaxel administration significantly inhibited tumor growth in 4T1-Neu tumor-bearing mice and considerably decreased MDSCs in vivo.The treatment selectively increased cytotoxic T lymphocyte (CTL) responses.Most importantly, docetaxel could directly modulate MDSC phenotype with preferential apoptosis of M2 cells and accumulation of M1 cells.These findings suggest that addition of docetaxel to current immunotherapeutic protocols could offer clinical benefit.
A piece of my mind. The smell of gardenias
Authors: C. A. Koller
Journal: JAMA (1994)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Highlights of This Issue
Journal: Clinical Cancer Research (2010)

The topoisomerase I inhibitor irinotecan is used for the treatment of advanced colorectal cancer. However, a low proportion of patients show an objective response to irinotecan, and biomarkers capable of predicting response to irinotecan are needed. Dopeso and colleagues found that colorectal cancer patients with low Aprataxin tumor levels had significantly longer overall survival (OS) following irinotecan treatment, compared to patients with high Aprataxin levels. The difference in OS between the groups was almost 1.5 years. These results suggest that Aprataxin levels could be used alone or in combination with other markers to make informed decisions regarding patient treatment.Success in treating metastatic renal cell carcinoma (RCC) with T cell–based therapies has been limited. Here, Leisegang and colleagues identified a highly specific T-cell receptor (TCR) able to recognize an HLAA2–restricted antigen shared by more than 60% of RCCs, without recognizing normal cell counterparts. Transgenic expression of the TCR in recipient lymphocytes (i.e. from patients) allowed large numbers of T cells with tumor-specific cytotoxicity and polyfunctional cytokine secretion to be generated in a short time period. Due to its specificity, this reagent has the potential to advance immunotherapeutic treatment of metastatic RCC.Cyclooxygenase-2 (COX-2) is a key enzyme involved in cancer development and progression, and elevated COX-2 expression is related to unfavorable survival after radiotherapy. In this issue, Bi and colleagues show that the COX-2-1195G/A polymorphism, which results in increased COX-2 expression, is independently associated with poor survival among inoperable locally advanced non–small cell lung cancer (NSCLC) patients treated with chemoradiotherapy or radiotherapy alone. These results suggest that the COX-2-1195G/A polymorphism may help to optimize cancer treatment by identifying different responders to COX-2–targeted therapy.Gene amplifications of both ERBB2 and TOP2A have been reported in breast cancer. In this study, Brase and colleagues performed a systematic analysis of both markers by investigating correlations between DNA amplification, gene expression, and protein expression, as well as studying their prognostic and predictive relevance. They found that TOP2A RNA levels were significantly associated with the metastasis-free survival interval (MFI) and good response to anthracyclin-based therapy. In contrast, ERBB2 gene expression was associated with the MFI only in ER-positive carcinomas and showed no association with response to treatment. These results suggest that TOP2A RNA level is an appropriate marker for prognostic and predictive purposes.
Rupture of the Aorta Due to Radiation Injury
Authors: Tung Pui Poon
Journal: JAMA (1968)

Necrotizing aortitis with rupture is a rare complication of radiation of mediastinal structure. To our knowledge, this is the first electron microscopic study of radiation changes of the aorta. Collagen fibers were preserved, but there was slit-like irregular fragmentation of elastic fibers. Marcias-Rojas and Castro<sup>1</sup>previously reported five cases of postradiation rupture of the aorta, all associated with mediastinitis. Our patient had an empyema. It is postulated that infection combined with radiation necrosis may have triggered the rupture.
POS0350 MicroRNAs ASSOCIATED WITH OSTEOPOROSIS IN PATIENTS WITH HAEMOCHROMATOSIS ARTHROPATHY
Authors: S. Finzel, A. Diendorfer, B. Butzeck, M. Hackl, R. Voll
Journal: Annals of the Rheumatic Diseases (2022)

Background Haemochromatosis arthropathy (HA) is one of the most frequent manifestations of hereditary haemochromatosis (HH). Moreover, frequency of osteoporosis is increased in HH. MicroRNAs (miRNAs) are small non-coding RNAs involved in gene silencing, and onset and progression of disease is often reflected in aberrant miRNA expression patterns including osteoarthritis and osteoporosis. Active or passive release of miRNAs from cells enables minimal-invasive detection in biofluids such as plasma (“circulating miRNAs”). Objectives We aimed to investigate whether circulating miRNAs involved in osteoporosis as well as liver disease in healthy elderly individuals are also elevated in patients with HH. Methods Plasma of 28 HA patients homozygeous for C282Y (60.71% female), 8 HA patients heterozygeous for C282Y (50% female), and 12 controls (66.67% female), was analyzed using the osteomiR and the hepatomiR RT-qPCR kits. Levels were normalized using spike-in controls and non-parametric analyses were performed to associate miRNAs to other clinical parameters and test for differential regulation of miRNAs between the groups. Results Even though mean age was different between the three groups (70.64, 52.38, 61.92 years), correlation analysis identified only weak or no associations to miRNA levels. In patients with osteoporosis (n=9, all female, all homozygeous) miR-203a-3p, 214-3p (both bone-related), and 122-5p (liver-related) were significantly downregulated (Kruskal Wallis p=0.024, p=0.037, and p=0.00024). Interestingly, miR-122-5p also showed a clear trend for down-regulation in homozygous HH compared to heterozygous HH and controls (p=0.087). Conclusion This is the first study reporting miRNAs involved in osteoporosis and liver diseases in patients homozygeous for C282Y. Disclosure of Interests None declared
Comment: The Basis for Selection of Hormonal Addition or Subtraction
Authors: Philip Rubin
Journal: JAMA (1967)

The stimulus for progressive proliferation in human breast cancer depends on the hormonal secretions which influence normal mammary growth. The alteration of the hormonal milieu is known to modify the proliferation pattern of tumor cells for varying periods of time. The difficulty is that 50% of all breast cancers are primarily hormone-independent and nonresponsive to hormone therapy, while an increasing proportion of hormone-dependent tumors develop secondary independence during their course.<sup>30</sup>The availability of modalities for varying the hormonal environment are many and the clinician managing the patient with disseminated cancer generally follows a scheme in which he sequentially selects the addition or subtraction of hormones. Let us examine the rationale for selection and study the physiologic vs the pragmatic factors influencing our choice. The primary axiom is alteration of the existent hormone state. The choice of ablative procedures in the premenopausal woman is logical in that hormone deprivation, specifically
The Causes of Cerebral Palsy
Authors: Vanja A. Holm
Journal: JAMA (1982)

In a retrospective review of cases, the causes of cerebral palsy in 142 children living in the northwestern United States and born after Jan 1, 1970, were prenatal in 50% of the cases, similar to findings recently reported from Sweden. The causes were perinatal in 33%, postnatal in 10%, and mixed in 7%. Epidemiologic studies from the 1950s report the origins of cerebral palsy to be mostly perinatal. The discrepancy is explained largely by differences in interpretation of medical findings prompted by recent advances in knowledge of fetal development and implications of obstetric and neonatal events. Cerebral palsy was considered medically preventable in 6% of full-term perinatal cases, possibly medically preventable in another 4%, and socially preventable in 4% of posttraumatic and 22% of preterm cases. Research in prenatal development, improvements in health education, and expansion of clinical genetic services are suggested as the most promising avenues toward prevention of cerebral palsy. (<i>JAMA</i>1982;247:1473-1477)
Spontaneous and Induced Metastasis of Naturally Occurring Tumors in Mice: Analysis of Cell Shedding Into the Blood&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1984)

The lung colonization capability (after iv inoculation) of each of 77 autochthonous virus-induced mammary tumors in C3H/Avy female mice was compared with its own spontaneous metastatic behavior. Twenty-four of these neoplasms had spontaneously metastasized to the lungs of the tumor bearer. The results were interpreted in the framework of dose-response studies on experimentally induced metastasis. These results indicate that tumors of high lung colonization potential (HCP) overgrow the lungs with iv doses as low as 104 cells, whereas tumors of low lung colonization potential (LCP) require at least 250 times this dose to achieve the same result. No general similarity was found between spontaneous and induced metastatic capability. Although some tumors showed good correspondence, others showed discrepancies and provided new information on mechanisms of cell shedding from primary tumors and on rate-limiting steps in metastasis. For example, from the dose-response studies, nonmetastatic tumors of HCP (iv) are deduced to be shedding very few cells. These findings suggest that escape from the primary tumor is an active process or else passive leakage of cells into vessels by hemorrhage, necrosis, or palpation should have resulted in spontaneous metastasis. Spontaneously metastatic tumors of LCP corroborate the view that metastasis is effected by a highly active subpopulation with special properties; otherwise, the required scale of passive cell release into the blood would be unrealistically large. Blood bioassay and timecourse studies on pulmonary deposit formation indicate that shedding of metastatic cells occurs early in mammary tumor development.
The Accuracy of Portable Cholesterol Analyzers in Public Screening Programs
Authors: Michelle J. Naughton
Journal: JAMA (1990)

To determine the accuracy of portable cholesterol analyzers in public settings, four screening organizations were accompanied to cholesterol screenings where consenting participants completed the finger-stick procedure and provided a blood sample by venipuncture. The finger-stick values were compared later with the participants' blood cholesterol values obtained in a reference laboratory. The results indicated that only one of the organizations produced cholesterol measurements entirely within the acceptable range ( ± 14.2%), while the accuracy of the other three organizations ranged from 76.5% to 96.4%. Those finger-stick values that did not fall within the acceptable range tended to underestimate the laboratory cholesterol values. Additionally, classification of the persons screened based on the National Cholesterol Education Program risk categories indicated that the finger-stick values primarily tended to produce false-negative results. The variability of the results across organizations was caused partially by insufficient operator training. However, inadequate quality-control procedures for field settings and dilution of capillary blood by tissue fluid also may have contributed to the inaccurate finger-stick results. (<i>JAMA</i>. 1990;263:1213-1217)
Depression of Natural Antitumor Resistance of C57BL/6 Mice by Leukemogenic Doses of Radiation and Restoration of Resistance by Transfer of Bone Marrow or Spleen Cells From Normal, But Not Beige, Syngeneic Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1982)

Small fractionated doses of radiation (4 weekly doses of 179 rad) induced leukemia in 93% of C57BL/6J mice. These leukemogenic doses of radiation were associated with suppression of natural killer (NK) cell activity, as assessed in vitro by cytotoxic activity of spleen cells or in vivo by the ability of irradiated mice to eliminate iv inoculated radiolabeled YAC-1 lymphoma cells. This suppressive effect of irradiation was profound and prolonged, being detectable for at least 7 weeks after the last dose of radiation. NK reactivity of irradiated C57BL/6 +/+ or C57BL/6 beige mice could be reconstituted by iv transfer of 10×106 bone marrow cells or 50×106 spleen cells from normal C57BL/6 mice. In contrast, transfer of bone marrow or spleen cells from beige donors did not change the NK reactivity of irradiated C57BL/6 +/+ or C57BL/6 bg/bg recipients. It was also shown that the irradiation protocol did not eliminate potentially reactive NK cells, because following interferon incubation (103 U/ml), the NK activity of spleen cells of irradiated mice was substantially increased. This study supports the hypothesis of an important role for NK cells in radiation-induced leukemogenesis and forms the basis for exploration of the needed, more direct data on the effects of reconstitution of NK activity on subsequent development of tumors.
Increased Porphobilinogen Deaminase Activity in Patients With Malignant Lymphoproliferative Diseases
Authors: Meir Lahav
Journal: JAMA (1987)

Patients with malignant lymphoproliferative diseases, ie, chronic lymphocytic leukemia and lymphoma, were found to have higher porphobilinogen deaminase (PBGD) activity in their peripheral lymphocytes than normal control subjects, patients with other malignant neoplasms, and patients with various infectious diseases. The specificity and sensitivity of the test were 99% and 87%, respectively. The sensitivity of the test was 100% in patients with chronic lymphocytic leukemia and 82% in patients with lymphoma. The diagnostic value of PBGD determinations was shown in a prospective study of a group of patients evaluated because of fever of unknown origin, anemia, or other constitutional symptoms with or without lymphadenopathy or a mediastinal mass. The positive and negative predictive values in these patients were 91% and 100%, respectively. Nearly all patients who were in remission had normal enzyme activity. Lymphocyte PBGD determinations also may be of value in determining when to terminate or reinitiate drug treatment. (<i>JAMA</i>1987;257:39-42)